Masked Continuous Glucose Monitoring Research Articles

Glycaemic Effects of a 156-km Ultra-trail Race in Athletes: An Observational Field Study.

Ultra-trail running races pose appreciable physiological challenges, particularly for glucose metabolism. Previous studies that yielded divergent results only measured glycaemia at isolated times. We aimed to explore the impact of an ultra-endurance race on continuously measured glycaemia and to understand potential physiological mechanisms, as well as the consequences for performance and behavioural alertness. Fifty-five athletes (78% men, 43.7 ± 9.6years) ran a 156-km ultra-trail race (six 26-km laps, total elevation 6000m). Participants wore a masked continuous glucose monitoring sensor from the day before the race until 10days post-race. Blood was taken at rest, during refuelling stops after each lap, and after 24-h recovery. Running intensity (% heart rate reserve), performance (lap times), psychological stress, and behavioural alertness were explored. Linear mixed models and logistic regressions were carried out. No higher risk of hypo- or hyperglycaemia was observed during the exercise phases of the race (i.e. excluding stops for scientific measurements and refuelling) compared with resting values. Laps comprising a greater proportion of time spent at maximal aerobic intensity were nevertheless associated with more time > 180mg/dL (P = 0.021). A major risk of hyperglycaemia appeared during the 48-h post-race period compared with pre-race (P < 0.05), with 31.9% of the participants spending time with values > 180mg/dL during recovery versus 5.5% during resting. Changes in circulating insulin, cortisol, and free fatty acids followed profiles comparable with those usually observed during traditional aerobic exercise. However, creatine phosphokinase, and to a lesser extent lactate dehydrogenase, increased exponentially during the race (P < 0.001) and remained high at 24-h post-race (P < 0.001; respectively 43.6 and 1.8 times higher vs. resting). Glycaemic metrics did not influence physical performance or behavioural alertness. Ultra-endurance athletes were exposed to hyperglycaemia during the 48-h post-race period, possibly linked to muscle damage and inflammation. Strategies to mitigate muscle damage or subsequent inflammation before or after ultra-trail races could limit recovery hyperglycaemia and hence its related adverse health consequences. NCT05538442 2022-09-21 retrospectively registered.

Continuous Glucose Monitoring Profiles and Health Outcomes after Dapagliflozin Plus Saxagliptin vs Insulin Glargine.

Glycemic variability and hypoglycemia during diabetes treatment may impact therapeutic effectiveness and safety, even when glycated hemoglobin (HbA1c) reduction is comparable between therapies. We employed masked continuous glucose monitoring (CGM) during a randomized trial of dapagliflozin plus saxagliptin (DAPA+SAXA) vs insulin glargine (INS) to compare glucose variability and patient-reported outcomes (PROs). 24-week sub-study of a randomized, open-label, two-arm, parallel-group, phase 3b study. Multicenter study (112 centers in 11 countries). 283 adults with type 2 diabetes (T2D) inadequately controlled with metformin ± sulfonylurea. DAPA+SAXA vs INS. Changes in CGM profiles, HbA1c, and PROs. Changes from baseline in HbA1c with DAPA+SAXA were similar to those observed with INS, with mean difference [95% CI] between decreases of -0.12% [-0.37 to 0.12%], P = .33. CGM analytics were more favorable for DAPA+SAXA, including greater percent time in range (> 3.9 and ≤ 10 mmol/L; 34.3 ± 1.9 vs 28.5 ± 1.9%, P = .033), lower percent time with nocturnal hypoglycemia (area under the curve ≤ 3.9 mmol/L; 0.6 ± 0.5 vs 2.7 ± 0.5%, P = .007), and smaller mean amplitude of glycemic excursions (-0.7 ± 0.1 vs -0.3 ± 0.1 mmol/L, P = .017). Improvements in CGM were associated with greater satisfaction, better body weight image, less weight interference, and improved mental and emotional well-being. DAPA+SAXA and INS were equally effective in reducing HbA1c at 24 weeks, but people with T2D treated with DAPA+SAXA achieved greater time in range, greater reductions in glycemic excursions and variability, less time with hypoglycemia, and improved patient-reported health outcomes.

Design of a randomized cross-over study evaluating effects of carbohydrate intake on glycemic control in persons with type 1 diabetes.

Diet is an important factor in managing glycemic control in type 1 diabetes (T1D). Reducing carbohydrate intake may be important for stabilizing blood glucose levels in certain groups of patients with T1D. There are few studies examining the effects of a low carbohydrate diet in patients with T1D. The aim of this study is to investigate the effects of carbohydrate intake on glucose control in adults with T1D. Adults with T1D (N = 54) and inadequate glycemic control (HbA1c ≥ 7.5%; 58 mmol/mol) were randomized in a cross-over design to a moderate carbohydrate diet (30 percent of total energy from carbohydrates) versus a traditional diabetes diet (50 percent of total energy from carbohydrates) for 4 weeks with a between wash-out period of 4 weeks. Masked continuous glucose monitoring was used throughout the study to evaluate effects on mean blood glucose levels, time-in-range, hypoglycemia, hyperglycemia, and glycemic variability. Diabetes treatment satisfaction, hypoglycemic confidence, and physical activity were measured using questionnaires during different phases of the trial. HbA1c, blood lipids, blood pressure, and ketone levels were also measured. The primary endpoint is the difference in mean blood glucose level between the diet periods. Study completion is anticipated during winter 2022. The study seeks to increase knowledge about the effects of dietary carbohydrate intake on glycemic control and other health parameters in patients with T1D. If beneficial effects on mean blood glucose level without elevated risk of hypoglycemia or ketoacidosis are shown, a moderate carbohydrate diet may be a treatment option for people with T1D that have unsatisfactory blood glucose levels.Clinical Trials Registration: www.clinicaltrials.gov, ID: NCT03400618.

Persistent post-bariatric-surgery hypoglycemia: A long-term follow-up reassessment

Background and aimPost-bariatric-surgery hypoglycemia (PBH) is a serious complication of bariatric surgery (BS). In our previous study about three quarters of the patients developed PBH. However long-term follow-up data is lacking to determine whether this condition improves with time. The aim of the current study was to re-assess post-BS patients who participated in our previous study and determine whether there are changes in the frequency and/or severity of hypoglycemic events. Methods and resultsTwenty-four post-BS, post Roux-en-Y gastric-bypass (RYGB = 10), post omega-loop gastric-bypass (OLGB = 9) and post sleeve-gastrectomy (SG = 5) individuals were reevaluated in a follow-up study 34.4 ± 4 months after their previous assessment and 67 ± 17 months since surgery. The evaluation included: a dietitian assessment, a questionnaire, meal-tolerance test (MTT) and a one-week masked continuous glucose monitoring (CGM). Hypoglycemia and severe hypoglycemia were defined by glucose levels ≤54 mg/dl and ≤40 mg/dl, respectively.Thirteen patients reported questionnaire meal-related complaints, mainly non-specific. During MTT, hypoglycemia occurred in 75% of the patients, and severe hypoglycemia in a third, but none was associated with specific complaints. During CGM, 66% of patients developed hypoglycemia and 37% had severe hypoglycemia. We did not observe significant improvements in hypoglycemic events compared to the previous assessment. Despite the high frequency of hypoglycemia, it did not necessitate hospitalizations or lead to death. ConclusionsPBH did not resolve within long-term follow-up. Intriguingly, most patient were unaware of these events which can lead to underestimation by the medical staff. Further studies are needed to determine possible long term sequela of repeated hypoglycemia.

Phase III, randomised, double-blind, placebo-controlled, multicentre trial to evaluate the efficacy and safety of rhGAD65 to preserve endogenous beta cell function in adolescents and adults with recently diagnosed type 1 diabetes, carrying the genetic HLA DR3-DQ2 haplotype: the DIAGNODE-3 study protocol

IntroductionType 1 diabetes (T1D) is an autoimmune disease leading to the destruction of the insulin-producing beta cells resulting in insulin deficiency and hyperglycaemic. Today, no approved therapy exists to halt...

Real-Time Continuous Glucose Monitoring Can Predict Severe Hypoglycemia in People with Type 1 Diabetes: Combined Analysis of the HypoDE and DIAMOND Trials

Objective: We combined data from two landmark trials (DIAMOND and HypoDE) to examine the diagnostic performance of low glucose measurements derived from open and masked continuous glucose monitoring (CGM) to predict the occurrence of future severe hypoglycemia (SH). Methods: We analyzed hypoglycemia parameters (low blood glucose index [LBGI], % <70 mg/dL, 54-69 mg/dL [level 1 hypoglycemia] and <54 mg/dL [level 2 hypoglycemia]) from masked CGM over 14 days during baseline and from open CGM over 14 days after randomization. We used receiver operating characteristics (ROC) curves to evaluate the screening performance of these measures to predict future SH. Positive likelihood ratios were calculated to indicate the overall diagnostic performance of these parameters. Results: Data from 288 individuals with type 1 diabetes (mean age 45.6 ± 12.8 years, diabetes duration 20.7 ± 13.7 years, HbA1c 8.2% ± 1.0%, Hypoglycemia Unawareness Score 3.4 ± 2.1) were analyzed. Area under ROC-curve (AUC) for LBGI and % <70 mg/dL ranged between 0.68 and 0.75, indicating that LBGI and % <70 mg/dL could significantly predict future SH. Significance of AUC regarding % <54 mg/dL were mixed (0.63-0.72). Positive and negative likelihood ratios ranged between 1.82 to 3.40 and 0.56 to 0.32, respectively. Suggested optimal cutoff values were remarkedly lower in open CGM than in masked CGM. Conclusion: These results indicate that CGM-derived hypoglycemic parameters have a good screening performance to significantly predict future clinical hypoglycemia. In addition, this analysis suggests that cutoff values to indicate elevated hypoglycemia risk in the future are substantially lower in open CGM than in masked CGM. ClinicalTrials.gov registration numbers: HypoDE: NCT02671968. DIAMOND: NCT02282397.

Driving with Type 1 Diabetes: Real-World Evidence to Support Starting Glucose Level and Frequency of Monitoring During Journeys.

There is limited evidence supporting the recommendation that drivers with insulin-treated diabetes need to start journeys with glucose >90 mg/dL. Glucose levels of drivers with type 1 diabetes were monitored for 3 weeks using masked continuous glucose monitoring (CGM). Eighteen drivers (median [IQR] age 40 [35, 51] years; 11 men) undertook 475 trips (duration 15 [13, 21] min). Hypoglycemia did not occur in any trip starting with glucose >90 mg/dL (92%; n = 436). Thirteen drivers recorded at least one trip (total n = 39) starting with glucose <90 mg/dL. Among these, driving glucose was <70 mg/dL in five drivers (38%) during 10 trips (26%). Among five drivers (28%), a ≥ 36 mg/dL drop was observed within 20 min of starting their journey. Journey duration was positively associated with maximum glucose change. These findings support current guidelines to start driving with glucose >90 mg/dL, and to be aware that glucose levels may change significantly within 20 min. A CGM-based, in-vehicle display could provide glucose information and alerts that are compatible with safe driving. Clinical Trial Registration number: ACTRN12617000520336.

Pramlintide for post-bariatric hypoglycaemia.

The aim of this study was to examine the hypothesis that pramlintide would reduce hypoglycaemia by slowing gastric emptying and reducing postprandial glucagon secretion, thus limiting postprandial glycaemic excursions and insulin secretion, and thus to determine the efficacy of pramlintide on frequency and severity of hypoglycaemia in post-bariatric hypoglycaemia (PBH). Participants with PBH following gastric bypass were recruited from outpatient clinics at the Joslin Diabetes Center, Boston, Massachusetts for an open-label study of pramlintide efficacy over 8 weeks. Twenty-three participants were assessed for eligibility, 20 participants had at least one pramlintide dose, and 14 completed the study. A mixed-meal tolerance test (MMTT) was performed at baseline and after 8 weeks of subcutaneous pramlintide with a sequential dose increase to a maximum of 120 micrograms (mean 69 ± 32 mcg) three times daily. The primary endpoint was change in glucose excursions during the MMTT. Secondary measures included MMTT insulin response, satiety and dumping score, percentage time with sensor glucose (SG) <3.9 mM, and number of days with minimum SG <3 mM, during masked continuous glucose monitoring. There were no differences in MMTT glucose, glucagon or insulin between baseline and post treatment. We observed no significant change in satiety or dumping scores. The overall frequency of low SG values did not change, although there was substantial inter-individual variability. In PBH, pramlintide does not modulate glycaemic or insulin responses, satiety, or dumping scores during an MMTT and does not impact glycaemic excursions or decrease low SG levels in the outpatient setting.

Use of Connected Pen as a Diagnostic Tool to Evaluate Missed Bolus Dosing Behavior in People with Type 1 and Type 2 Diabetes.

Objective: This study used connected pen to determine missed bolus dose (MBD) frequency during masked and unmasked continuous glucose monitoring (CGM) periods and examined its link with time-in-range (TIR), time-above-range (TAR), time-below-range (TBR), and key participant characteristics in people with diabetes.Methods: This was a 12-week, single-arm, exploratory, two-period study for people with type 1 diabetes (T1D) or type 2 diabetes (T2D). The primary objective was to estimate the average number of MBD during masked and real-time CGM use. The secondary objective was to estimate the average percent TIR and its relationship to MBD. An exploratory objective was to investigate the participant characteristics that were associated with MBD. Data were analyzed for differences in MBD by diabetes type and other participant characteristics, by CGM period, and by hypoglycemic fear scores.Results: Participants (n = 64; T1D, n = 38; T2D, n = 26) were 48 ± 11.9 years old and 44% were female. From the masked to the unmasked period, MBD, %TAR, %TBR, and glycated hemoglobin decreased significantly (0.74 MBD/day to 0.62 MBD/day, P = 0.008; 53.6%–48.1%, P = 0.004; 4.49%–2.93%, P < 0.001; mean 8.8%–8.4%, P < 0.001, respectively), while %TIR increased significantly (41.9%–49.0%, P < 0.001). MBD/day was negatively associated with TIR (P = 0.016) and positively associated with TAR (P = 0.015) for T1D and positively associated with TBR (P = 0.024) for T2D in the masked period only. MBD was significantly associated with fear of hypoglycemia for T2D, but not T1D.Conclusions: MBD is associated with reduced TIR when CGM is masked and tailored therapeutic approaches are needed for T1D and T2D populations.

Effect of a Hybrid Closed-Loop System on Glycemic and Psychosocial Outcomes in Children and Adolescents With Type 1 Diabetes

Hybrid closed-loop (HCL) therapy has improved glycemic control in children and adolescents with type 1 diabetes; however, the efficacy of HCL on glycemic and psychosocial outcomes has not yet been established in a long-term randomized clinical trial. To determine the percentage of time spent in the target glucose range using HCL vs current conventional therapies of continuous subcutaneous insulin infusion or multiple daily insulin injections with or without continuous glucose monitoring (CGM). This 6-month, multicenter, randomized clinical trial included 172 children and adolescents with type 1 diabetes; patients were recruited between April 18, 2017, and October 4, 2019, in Australia. Data were analyzed from July 25, 2020, to February 26, 2021. Eligible participants were randomly assigned to either the control group for conventional therapy (continuous subcutaneous insulin infusion or multiple daily insulin injections with or without CGM) or the intervention group for HCL therapy. The primary outcome was the percentage of time in range (TIR) within a glucose range of 70 to 180 mg/dL, measured by 3-week masked CGM collected at the end of the study in both groups. Secondary outcomes included CGM metrics for hypoglycemia, hyperglycemia, and glycemic variability and psychosocial measures collected by validated questionnaires. A total of 135 patients (mean [SD] age, 15.3 [3.1] years; 76 girls [56%]) were included, with 68 randomized to the control group and 67 to the HCL group. Patients had a mean (SD) diabetes duration of 7.7 (4.3) years and mean hemoglobin A1c of 64 (11) mmol/mol, with 110 participants (81%) receiving continuous subcutaneous insulin infusion and 72 (53%) receiving CGM. In the intention-to-treat analyses, TIR increased from a mean (SD) of 53.1% (13.0%) at baseline to 62.5% (12.0%) at the end of the study in the HCL group and from 54.6% (12.5%) to 56.1% (12.2%) in the control group, with a mean adjusted difference between the 2 groups of 6.7% (95% CI, 2.7%-10.8%; P = .002). Hybrid closed-loop therapy also reduced the time that patients spent in a hypoglycemic (<70 mg/dL) range (difference, -1.9%; 95% CI, -2.5% to -1.3%) and improved glycemic variability (coefficient of variation difference, -5.7%; 95% CI, -10.2% to -0.9%). Hybrid closed-loop therapy was associated with improved diabetes-specific quality of life (difference, 4.4 points; 95% CI, 0.4-8.4 points), with no change in diabetes distress. There were no episodes of severe hypoglycemia or diabetic ketoacidosis in either group. In this randomized clinical trial, 6 months of HCL therapy significantly improved glycemic control and quality of life compared with conventional therapy in children and adolescents with type 1 diabetes. ANZCTR identifier: ACTRN12616000753459.

699-P: Prerandomization Factors Associated with Time-in-Target Glucose Range with Hybrid Closed-Loop Use in a Six-Month Randomized Controlled Trial in Adults with Type 1 Diabetes

Background: In our published trial in 120 adults with type 1 diabetes (T1D), allocation to hybrid closed loop (HCL) increased Continuous Glucose Monitoring (CGM) Time in Range ((TIR), 70-180mg/dL) by 15 percentage points vs. user-determined insulin dosing. Recommended TIR is >70%. Objective: To examine associations of pre-randomization factors with trial-end 3-weeks masked CGM TIR in adults with T1D treated with 6-months HCL. Methods: MDI and non-HCL pump users (no CGM) were randomized 1:1 to 26-weeks HCL (Medtronic 670G) or ongoing standard care. Analyses are on HCL group (n=55): Pre-randomization factors are related to trial-end masked CGM TIR >70 vs. ≤70% and to TIR as a continuous variable. Continuous variables are compared by t-test and binary variables by chi-square with significance at P Results: Table: Pre-randomization characteristics by trial-end TIR > vs. ≤70%. Significant univariate correlations between trial-end TIR as a continuous variable existed for pre-randomization factors: HbA1c (at enrolment and randomization), 1,5-anhydroglucitol, CGM metrics: %TIR (70-180mg/dl), %TIR (70-140mg/dl), mean glucose, SD glucose. Conclusions: The main factor associated with HCL users achieving higher TIR was pre-randomization glycemia. TIR was not associated with age, sex, prior pump use and socioeconomic status. Disclosure A. Jenkins: Advisory Panel; Self; Abbott Diabetes, Sanofi-Aventis, Other Relationship; Self; Amgen Inc., Research Support; Self; Abbott, International Diabetes Federation, JDRF, Medtronic, Mylan N. V. N. Cohen: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Research Support; Self; Ypsomed Group, Speaker’s Bureau; Self; Novo Nordisk. P. G. Colman: None. E. A. Davis: None. J. Holmes-walker: None. A. C. Keech: None. R. Macisaac: Advisory Panel; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Novo Nordisk, Servier Laboratories, Speaker’s Bureau; Self; Boehringer Ingelheim International GmbH, Novo Nordisk. C. M. Sims: Stock/Shareholder; Self; Medtronic. V. Sundararajan: None. S. Trawley: None. G. M. Ward: None. A. S. Januszewski: None. T. Jones: None. D. N. O’neal: Advisory Panel; Self; Abbott Diabetes, Medtronic, Sanofi, Research Support; Self; Dexcom, Inc., GlySens Incorporated, Medtronic, Pacific Diabetes Technologies. Jdrf australia adult hybrid closed loop trial: n/a. A. Kirby: None. S. A. Mcauley: Speaker’s Bureau; Self; Sanofi. M. H. Lee: None. B. Paldus: Speaker’s Bureau; Self; Medtronic. S. Vogrin: None. M. De bock: None. M. Burt: None. Funding JDRF (3-SRA-2016-351-M-B)

Glycemic Patterns Are Distinct in Post-Bariatric Hypoglycemia After Gastric Bypass (PBH-RYGB).

Severe hypoglycemia with neuroglycopenia, termed post-bariatric hypoglycemia (PBH). typically occurs postprandially, but it is also reported after activity or mid-nocturnally. To quantify glycemia, glycemic variability, and magnitude/duration of low sensor glucose (SG) values in patients with PBH after Roux-en-Y gastric bypass (PBH-RYGB). This retrospective analysis of data from an academic medical center included individuals with PBH-RYGB (n = 40), reactive hypoglycemia without gastrointestinal surgery (Non-Surg Hypo, n = 20), prediabetes (Pre-DM, n = 14), newly diagnosed T2D (n = 5), and healthy controls (HC, n = 38). Masked continuous glucose monitoring (Dexcom G4) was used to assess patterns over 24 hours, daytime (6 am-midnight) and nighttime (midnight-6 am). Prespecified measures included mean and median SG, variability, and percent time at thresholds of sensor glucose. Mean and median SG were similar for PBH-RYGB and HC (mean: 99.8 ± 18.6 vs 96.9 ± 10.2 mg/dL; median: 93.0 ± 14.8 vs 94.5 ± 7.4 mg/dL). PBH-RYGB had a higher coefficient of variation (27.3 ± 6.8 vs 17.9 ± 2.4%, P < 0.0001) and range (154.5 ± 50.4 vs 112.0 ± 26.7 mg/dL, P < 0.0001). Nadir was lowest in PBH-RYGB (42.5 ± 3.7 vs HC 49.0 ± 11.9 mg/dL, P = 0.0046), with >2-fold greater time with SG < 70 mg/dL vs HC (7.7 ± 8.4 vs 3.2 ± 4.1%, P = 0.0013); these differences were greater at night (12.6 ± 16.9 vs 1.0 ± 1.5%, P < 0.0001). Non-Surg Hypo also had 4-fold greater time with SG < 70 at night vs HC (SG < 70: 4.0 ± 5.9% vs 1.0 ± 1.5%), but glycemic variability was not increased. Patients with PBH-RYGB experience higher glycemic variability and frequency of SG < 70 compared to HC, especially at night. These data suggest that additional pathophysiologic mechanisms beyond prandial changes contribute to PBH.

Real-time continuous glucose monitoring in preterm infants (REACT): an international, open-label, randomised controlled trial

SummaryBackgroundHyperglycaemia and hypoglycaemia are common in preterm infants and have been associated with increased risk of mortality and morbidity. Interventions to reduce risk associated with these exposures are particularly challenging due to the infrequent measurement of blood glucose concentrations, with the potential of causing more harm instead of improving outcomes for these infants. Continuous glucose monitoring (CGM) is widely used in adults and children with diabetes to improve glucose control, but has not been approved for use in neonates. The REACT trial aimed to evaluate the efficacy and safety of CGM in preterm infants requiring intensive care.MethodsThis international, open-label, randomised controlled trial was done in 13 neonatal intensive care units in the UK, Spain, and the Netherlands. Infants were included if they were within 24 h of birth, had a birthweight of 1200 g or less, had a gestational age up to 33 weeks plus 6 days, and had parental written informed consent. Infants were randomly assigned (1:1) to real-time CGM or standard care (with masked CGM for comparison) using a central web randomisation system, stratified by recruiting centre and gestational age (<26 or ≥26 weeks). The primary efficacy outcome was the proportion of time sensor glucose concentration was 2·6–10 mmol/L for the first week of life. Safety outcomes related to hypoglycaemia (glucose concentrations <2·6 mmol/L) in the first 7 days of life. All outcomes were assessed on the basis of intention to treat in the full analysis set with available data. The study is registered with the International Standard Randomised Control Trials Registry, ISRCTN12793535.FindingsBetween July 4, 2016, and Jan 27, 2019, 182 infants were enrolled, 180 of whom were randomly assigned (85 to real-time CGM, 95 to standard care). 70 infants in the real-time CGM intervention group and 85 in the standard care group had CGM data and were included in the primary analysis. Compared with infants in the standard care group, infants managed using CGM had more time in the 2·6–10 mmol/L glucose concentration target range (mean proportion of time 84% [SD 22] vs 94% [11]; adjusted mean difference 8·9% [95% CI 3·4–14·4]), equivalent to 13 h (95% CI 5–21). More infants in the standard care group were exposed to at least one episode of sensor glucose concentration of less than 2·6 mmol/L for more than 1 h than those in the intervention group (13 [15%] of 85 vs four [6%] of 70). There were no serious adverse events related to the use of the device or episodes of infection.InterpretationReal-time CGM can reduce exposure to prolonged or severe hyperglycaemia and hypoglycaemia. Further studies using CGM are required to determine optimal glucose targets, strategies to obtain them, and the potential effect on long-term health outcomes.FundingNational Institute for Health Research Efficacy and Mechanisms Evaluation Programme.

Less Nocturnal Hypoglycemia but Equivalent Time in Range Among Adults with Type 1 Diabetes Using Insulin Pumps Versus Multiple Daily Injections.

Background: This prerandomization analysis from the Australian HCL-Adult trial (registration number: ACTRN12617000520336) compared masked continuous glucose monitoring (CGM) metrics among adults using insulin pumps versus multiple daily injections (MDIs), who were all self-monitoring blood glucose (SMBG). Methods: Adults with type 1 diabetes, using an insulin pump or MDIs without real-time CGM (and entering a trial of closed-loop technology), were eligible. MDI users were given an insulin dosage calculator. All participants received diabetes and carbohydrate-counting education, then wore masked CGM sensors for 3 weeks. Ethics Approval: HREC-D 088/16 Results: Adults using MDIs (n = 61) versus pump (n = 59) did not differ by age, sex, diabetes duration, insulin total daily dose, or HbA1c at baseline. After education, median (interquartile range) CGM time in range (TIR) 70-180 mg/dL (3.9-10.0 mmol/L) was 54% (47, 62) for those using MDIs and 56% (48, 66) for those using pump (P = 0.40). All CGM metrics were equivalent for 24 h/day for MDI and pump users. Overnight, those using MDIs (vs. pump) spent more time with glucose <54 mg/dL (<3.0 mmol/L): 1.4% (0.1, 5.1) versus 0.5% (0.0, 2.0), respectively (P = 0.012). They also had more CGM hypoglycemia episodes (121 vs. 54, respectively; incidence rate ratio [95% confidence interval] 2.48 [1.51, 4.06]; P < 0.001). Conclusions: Adults with type 1 diabetes using pumps versus MDIs in conjunction with SMBG experienced less nocturnal hypoglycemia, measured by masked CGM, after equivalent diabetes and dietary education in conjunction with insulin dosage calculator provision to all. However, both groups had equivalent TIR. This observation may reflect advantages afforded by flexibility in basal insulin delivery provided by pumps.

Characteristics of Continuous Glucose Monitoring Metrics in Persons with Type 1 and Type 2 Diabetes Treated with Multiple Daily Insulin Injections

Although guidelines advocate similar CGM targets for insulin-treated persons with type 1 and type 2 diabetes, it is unclear how these persons differ with respect to hypoglycaemia, glucose variability and other CGM metrics in clinical practice. Methods; We used data from two multicenter randomized controlled trials (GOLD and MDI-Liraglutide) where 161 persons with type 1 diabetes and 124 persons with type 2 diabetes treated with multiple daily injections were included and monitored with masked CGM. Persons from both cohorts had similar mean glucose levels, 10.9 mmol/l (196 mg/dL) in persons with type 1 diabetes and 10.8 mmol/l (194 mg/dL) in persons with type 2 diabetes. Time in hypoglycemia (<3.9 mmol/l (70 mg/dL) was 5.1% and 1.0 % for persons with type 1 and type 2 diabetes, respectively (p<0.001). Corresponding estimates for the standard deviations of mean glucose levels were 4.4 mmol/l (79 mg/dL) vs 3.0 (54 mg/dL) (p<0.001), for CV 41% vs 28% (p<0.001) and for time in range 38.2% vs 45.3%, respectively (p=0.004). Mean C-peptide levels were 0.05 nmol/l and 0.67 nmol/l (p<0.001) for persons with type 1 and type 2 diabetes, respectively. Persons with type 1 diabetes compared to persons with type 2 diabetes treated with multiple daily injections spend considerably more time in hypoglycemia, have higher glucose variability, and less "Time in range". This needs to be taken into account in daily clinical care and in recommended targets for CGM metrics.

Glucose Variability and Time in Range in Type 2 Diabetes Treated with U-500R by Pump or Injection: CGM Findings from the VIVID Study.

Background: The EValuating U-500R Infusion Versus Injection in Type 2 Diabetes Mellitus (VIVID) study compared two methods of U-500R insulin delivery, continuous subcutaneous insulin infusion (CSII) and multiple daily injection (MDI), for 26 weeks in people with type 2 diabetes (T2D) requiring high doses of insulin. To assess glycemic variability (GV) and time in range (TIR), a subset of participants performed masked continuous glucose monitoring (CGM). Methods: VIVID participants were adults who had insulin requirements of >200 but ≤600 U/day and A1C 7.5% to 12%. Participants performed masked CGM for seven consecutive days on each of three occasions: before weeks 0 (baseline), 14, and 26. The primary objective was to compare GV between CSII and MDI groups, based on change from baseline of within-day standard deviation (SDw) of CGM glucose. Results: Of 54 participants enrolled, 41 with evaluable data were analyzed (17 and 24 in CSII and MDI groups, respectively). The CSII group had a significantly greater reduction from baseline in mean SDw of glucose (45.0 to 38.2 mg/dL [-8.1 mg/dL]) compared with the MDI group (47.0 to 45.8 [-0.4 mg/dL]; P = 0.047). TIR 70-180 mg/dL glucose increased significantly from baseline in the CSII group only, from 59.8% to 73.1% (change +12.9%, P < 0.05), but was not significantly different between groups. There were no significant between-group differences in the endpoint mean glucose or A1C. Conclusions: In the VIVID CGM substudy of U-500R in people with T2D requiring high doses of insulin, participants using CSII significantly reduced GV compared with MDI. CSII also significantly increased TIR with no difference between groups.

105-LB: Evening Oral Insulin (ORMD-0801) Glycemic Effects in Uncontrolled T2DM Patients

ORMD-0801 is a novel oral human insulin formulated to increase hepatic insulin exposure, and subsequently reduce hepatic glucose production and improve glycemic control, with minimal hypoglycemia risk. In a recently completed randomized, placebo-controlled, multicenter, phase 2b, 12-week study, 354 subjects with T2DM uncontrolled by multiple oral antidiabetic drugs and with HbA1c levels ≥7.5%, received placebo or 8 mg, 16 mg or 32 mg ORMD-0801 capsules up to three times daily. Masked continuous glucose monitoring was performed during a 14-day run-in period and over the last 14 days of treatment. HbA1c levels improved from baseline for most active treatment regimens, with largest improvements recorded in the 8 mg once daily (QD) and twice daily (BID) cohorts. Glucose AUC improved from baseline following 8 mg or 32 mg QD and all tested BID treatments and was most pronounced in patients receiving 8 mg QD at bedtime. Hypoglycemia event rates were low and similar to the placebo arm. Body weight remained stable in all treatment arms and frequency of drug-related adverse events was similar across cohorts. In summary, ORMD-0801 elicited clinically significant HbA1c reductions in poorly controlled T2DM patients on standard therapies and with mean HbA1c levels &amp;gt;8%, without increasing hypoglycemia rate or weight. The 8 mg QD regimen appears most effective, warranting further studies to confirm the efficacy of this once daily evening dose. Disclosure R. Eldor: Advisory Panel; Self; Oramed. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Medtronic, Merck Sharp &amp; Dohme Corp., Novo Nordisk Inc., Sanofi. Stock/Shareholder; Self; Oramed. G. Fleming: Consultant; Self; ADOCIA, Biocon, Caladrius Biosciences, Inc., Dance Biopharm Holdings, Inc., Diasome Pharmaceuticals, Inc., Intarcia Therapeutics, MannKind Corporation, NuSirt Biopharma, Inc., Oramed Pharmaceuticals, Sanofi, Tolerion, Inc. J. Neutel: None. K.E. Homer: None. M. Kidron: Employee; Self; Oramed Pharmaceuticals. Stock/Shareholder; Self; Oramed Pharmaceuticals. J. Rosenstock: Research Support; Self; AstraZeneca, Bristol-Myers Squibb, Genentech, Inc., GlaxoSmithKline plc., Lexicon Pharmaceuticals, Inc., Oramed Pharmaceuticals, PegBio Co., Ltd., Pfizer Inc., REMD Biotherapeutics. Other Relationship; Self; Applied Therapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi.

67-OR: Benefit of Reduced Hypoglycemia with Continuous Glucose Monitoring (CGM) Is Sustained through 12 Months among Young Children with Type 1 Diabetes (T1D)

The SENCE study in children &amp;lt; 8 yrs with T1D compared the efficacy of CGM combined with a family behavioral intervention (CGM + FBI) and CGM alone (Standard-CGM) with blood glucose monitoring (BGM) alone. Time in hypoglycemia fell in both CGM groups but was unaffected in the BGM group during the 26-week trial. After trial completion, both CGM groups extended their time on CGM for 26 weeks without additional education/behavioral intervention. This analysis assessed whether prolonged CGM use maintained durable reductions in time in hypoglycemia throughout the entire 52-week period. The extended study was completed by 45 of 50 in the CGM + FBI group and 42 of 44 in Standard-CGM. In these 87 kids, median age was 5.6 years and 31% were on insulin pumps. Differences in the two CGM groups were compared to masked baseline CGM data from run-in. Median time &amp;lt;70 mg/dL was reduced from baseline to 52 weeks in CGM+FBI group (3.4%,50 minutes/day to 2.0%, 29 minutes/day, p&amp;lt;0.001, see Figure) and with Standard-CGM (4.1%, 59 minutes/day, to 2.1%, 30 minutes/day, p&amp;lt;0.001). Importantly, time in hypoglycemia remained lower after conclusion of the interventions through 52 weeks in both groups. We observed similar reductions for time &amp;lt;54 mg/dL (data not shown). Conclusion: Sustained CGM use results in less hypoglycemia in young children with T1D. Disclosure M.A. Van Name: None. K. Miller: None. L. Kanapka: None. W.V. Tamborlane: Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Novo Nordisk Inc., Sanofi US. Other Relationship; Self; Eisai Inc., MannKind Corporation. L. DiMeglio: None. Funding The Leona M. and Harry B. Helmsley Charitable Trust

Assessing the effect of closed-loop insulin delivery from onset of type 1 diabetes in youth on residual beta-cell function compared to standard insulin therapy (CLOuD study): a randomised parallel study protocol

IntroductionManagement of newly diagnosed type 1 diabetes (T1D) in children and adolescents is challenging for patients, families and healthcare professionals. The objective of this study is to determine whether continued...

Effect of Liraglutide on Times in Glycaemic Ranges as Assessed by CGM for Type 2 Diabetes Patients Treated With Multiple Daily Insulin Injections

IntroductionThe effects of the GLP-1 analogue liraglutide on time in hypoglycaemia, time in hyperglycaemia, and time in range for type 2 diabetes patients initially treated with multiple daily insulin injections (MDI) were investigated. Variables associated with hypoglycaemia in the current population were also identified.MethodsAnalyses were based on data from a previously performed double-blind, placebo-controlled trial in which 124 MDI-treated patients with type 2 diabetes were randomized to liraglutide or placebo. Masked continuous glucose monitoring (CGM) was performed at baseline and week 24 in 99 participants.ResultsThe mean time in hypoglycaemia was similar for participants receiving liraglutide and those receiving placebo after 24 weeks of treatment. Mean time in target was greater in the liraglutide group than in the placebo group: 430 versus 244 min/24 h (p < 0.001) and 960 versus 695 min/24 h (p < 0.001) for the two glycaemic ranges considered, 4–7 mmol/l and 4–10 mmol/l, respectively. Mean time in hyperglycaemia was lower in the liraglutide group: 457 versus 723 min/24 h (p = 0.001) and 134 versus 264 min/24 h (p = 0.023) for the two cutoffs considered, > 10 mmol/l and > 14 mmol/l, respectively. Lower mean glucose level, lower C-peptide, and higher glucose variability were associated with an increased risk of hypoglycaemia in both treatment groups. Higher proinsulin level was associated with a lower risk of hypoglycaemia in the liraglutide group.ConclusionFor type 2 diabetes patients initially treated with MDI, introducing liraglutide had a beneficial effect on glucose profiles estimated by masked CGM. Mean glucose level, glycaemic variability, C-peptide, and proinsulin level influenced the risk of hypoglycaemia in this population.Trial RegistrationClinicalTrials.gov, number (EudraCT nr: 2012-001941-42).FundingNovo Nordisk funded this study. The Diabetes Research Unit, NU-Hospital Group funded the journal’s Rapid Service Fee.Electronic Supplementary MaterialThe online version of this article (10.1007/s13300-019-00692-1) contains supplementary material, which is available to authorized users.